PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Community-Nominated Targets
July 2015
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Signaling with DivL
May 2015
Signaling: A Platform for Opposing Functions
May 2015
Signaling: Securing Lipid-Protein Partnership
May 2015
Dynamic DnaK
March 2015
Iron-Sulfur Cluster Biosynthesis
December 2014
Mitochondrion: Flipping for UCP2
December 2014
Mitochondrion: Setting a New TRAP1
December 2014
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Quorum Sensing: E. coli Gets Involved
August 2014
iTRAQing the Ubiquitinome
July 2014
Microbiome: The Dynamics of Infection
September 2013
Protein-Nucleic Acid Interaction: A Modified SAM to Modify tRNA
July 2013
Protein-Nucleic Acid Interaction: Versatile Glutamate
July 2013
PDZ Domains
April 2013
Alpha-Catenin Connections
March 2013
Cell-Cell Interaction: A FERM Connection
March 2013
Cell-Cell Interaction: Magic Structure from Microcrystals
March 2013
Cell-Cell Interaction: Modulating Self Recognition Affinity
March 2013
Bacterial Hemophores
January 2013
Archaeal Lipids
December 2012
Membrane Proteome: Capturing Multiple Conformations
December 2012
Lethal Tendencies
October 2012
Symmetry from Asymmetry
October 2012
A signal sensing switch
September 2012
Regulatory insights
September 2012
AlkB Homologs
August 2012
Budding ensemble
August 2012
Targeting Enzyme Function with Structural Genomics
July 2012
The machines behind the spindle assembly checkpoint
June 2012
Chaperone interactions
April 2012
Pilus Assembly Protein TadZ
April 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Twist to open
March 2012
Disordered Proteins
February 2012
Analyzing an allergen
January 2012
Making Lipopolysaccharide
January 2012
Pulling on loose ends
January 2012
Terminal activation
December 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
TLR4 regulation: heads or tails?
October 2011
Ribose production on demand
September 2011
Moving some metal
August 2011
Looking for lipids
July 2011
Ribofuranosyl Binding Protein
June 2011
A molecular switch for neuronal growth
May 2011
Cell wall recycler
May 2011
Added benefits
April 2011
NMR challenges current protein hydration dogma
March 2011
Nitrile Reductase QueF
March 2011
Tip formin
March 2011
Inhibiting factor
February 2011
PASK staying active
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
December 2010
Function following form
October 2010
tRNA Isopentenyltransferase MiaA
August 2010
Importance of extension for integrin
June 2010
April 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Hemolysin BL
January 2010
December 2009
Two-component signaling
December 2009
Network coverage
November 2009
Pseudouridine Synthase TruA
November 2009
Unusual cell division
October 2009
Toxin-antitoxin VapBC-5
September 2009
Salicylic Acid Binding Protein 2
August 2009
Proofreading RNA
July 2009
Ykul structure solves bacterial signaling puzzle
July 2009
Hda and DNA Replication
June 2009
Controlling p53
May 2009
Mitotic checkpoint control
May 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
March 2009
High-energy storage system
February 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Poly(A) RNA recognition
January 2009
Activating BAX
December 2008
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
New metal-binding domain
October 2008
Blocking AmtB
September 2008
September 2008
Aspartate Dehydrogenase
August 2008
RNase T
July 2008
May 2008

Research Themes Cell biology

Hda and DNA Replication

PSI-SGKB [doi:10.3942/psi_sgkb/fm_2009_6]
Featured System - June 2009
Short description: Cell division requires careful bookkeeping.

Cell division requires careful bookkeeping. When they divide, our cells need to ensure that each daughter cell gets one copy of each chromosome. Bacteria face a similar, albeit simpler, problem. They contain a big circle of DNA, so they start replication one place, then copy the DNA both ways around the circle until it finishes on the other side. So, the challenge is to initiate replication at this origin only once for each generation of the cell. Researchers at the PSI JCSG have obtained the first atomic look at how bacteria use the Hda protein to solve this challenge.

Initiating Replication

The story starts with the DnaA protein, shown here from PDB entry 2hcb, which gets replication started in the right place. It binds to a special origin of replication on the DNA and forms a large helical assembly with the DNA wrapped around the outside. With the help of a few DNA-bending proteins, this is enough to disrupt the DNA double helix in a special region that is rich in AT base pairs. When this region unwinds, the DNA replication machinery binds and gets to work.

Once and Only Once

Once replication starts, several regulatory methods ensure that other DNA polymerases are blocked, so that the cell does not immediately start a second round of replication. The Hda protein, shown here from PDB entry 3bos, plays a central role in this regulation by disrupting the DnaA protein complex. When Hda is activated by one of the components of the DNA polymerase (indicating that replication has already begun), it binds to DnaA and cleaves a bound ATP (shown here in red). This causes the DnaA complex to fall apart. The DnaA proteins must then replace their ATP and form a new complex on the DNA before replication can start again.

Bending the Rules

It's important that cells only start replication once per generation, so that the daughter cells don't end up with extra copies of the genome. Bacterial cells, however, are very tricky and have figured out a way to divide faster than you would think was possible. For instance, an Escherichia coli cell typically requires about 40 minutes to replicate its DNA. However, in ideal environmental conditions, these same bacterial cells rapidly build new proteins, ribosomes and membranes and are seen to divide every 23 minutes. So how do they deal with their slow replication of DNA, since each new cell needs a copy? They do this by starting a new replication cycle each generation, even if the circle isn't completely copied yet. So, there may be several replication forks working on the DNA at any time, but only one completed cycle of replication each generation.

The JSmol tab below displays an interactive JSmol.

Salicylic Acid Binding Protein 2 (PDB entry 1y7i)

The active site of SABP2 completely surrounds the substrate. In this structure, the product salicylic acid is bound in the active site. The catalyic triad (serine 81, histidine 238 and aspartate 210) is shown with thick bonds and the rest of the protein chain is shown in dark green. Use the buttons below to display the collection of hydrophobic amino acids that surround the aromatic ring of salicylic acid.


  1. Xu, Q., McMullan, D., Abdubek, P., Astakhova, T., Carlton, D. Chen, C., Chiu, H.J., Clayton, T. Das, D. Deller, M. C., Duan, L., Elsliger, M. A., Feuerhelm, J., Hale, J., Han. G. W., Jaroszewski, L., Jin, K. K., Johnson, H. A., Klock, H. E., Knuth, M .W., Kozbial, P., Krishna, S. S., Kumar, A., Marciano, D., Miller, M. D., Morse, A. T., Nigoghossian, E., Nopakun, A., Okach, L., Oommachen, S., Paulsen, J., Puckett, C., Reyes, R., Rife, C. L., Sefcovic, N., Trame, C., van den Bedem, H., Weekes, D., Hodgson, K. O., Wooley, J., Deacon, A. M., Godzik, A., Lesley, S. A. and Wilson, I. A. (2009) A structural basis for the regulatory inactivation of DnaA. J. Mol. Biol. 385, 368-380.

  2. Nielsen, O. and Lobner-Olesen, A. (2008) Once in a lifetime: strategies for preventing re-replication in prokaryotic and eukaryotic cells. EMBO Reports 9, 151-156.

  3. Erzberger, J. P., Mott, M. L. and Berger, J. M. (2006) Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling. Nature Struc. Mol. Biol. 13, 676-683.

  4. Neidhardt, F. C., Ingraham, J. L. and Schaechter, M. (1990) Physiology of the bacterial cell. Sinauer Associates, Sunderland MA.

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health